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A single, large deletion accounts for all the beta-globin gene mutations in twenty families from Sabah (North Borneo), Malaysia. Mutation in brief no. 240. Online

Thong MK, Rudzki Z, Hall J, Tan JA, Chan LL, Yap SF

Hum Mutat, 1999;13(5):413.
PMID: 10338100 DOI: 10.1002/(SICI)1098-1004(1999)13:5<413::AID-HUMU15>

Beta-thalassemia major is one of the commonest genetic disorders in South-East Asia. The spectrum of beta-thalassemia mutations in the various ethnic sub-populations on the island of Borneo is unknown. We studied 20 Dusun children from the East Malaysian state of Sabah (North Borneo) with a severe beta-thalassemia major phenotype, using a combination of Southern analysis, polymerase chain reaction analysis and direct sequencing. We found the children to be homozygous for a large deletion, which has a 5' breakpoint at position -4279 from the cap site of the beta-globin gene (HBB) with the 3' breakpoint located in a L1 family of repetitive sequences at an unknown distance from the beta-globin gene. This was similar to a recent finding of a large deletion causing beta-thalassemia first described in unrelated beta-thalassemia heterozygotes of Filipino descent. This report describes the first 20 families with homozygosity of the deletion causing a severe phenotype. It provides the first information on the molecular epidemiology of beta-thalassemia in Sabah. This finding has implications for the population genetics and preventative strategies for beta-thalassemia major for nearly 300 million individuals in South-East Asia.
Age, sex, haemoglobin level, and white cell count at diagnosis are important prognostic factors in children with acute lymphoblastic leukemia treated with BFM-type protocol

Ng SM, Lin HP, Ariffin WA, Zainab AK, Lam SK, Chan LL

J Trop Pediatr, 2000 Dec;46(6):338-43.
PMID: 11191144

The presenting features and treatment outcome for 575 Malaysian children (< or = 12 years of age) with newly diagnosed acute lymphoblastic leukemia (ALL), admitted to the University Hospital, Kuala Lumpur, Malaysia between 1 January 1980 and 30 May 1995 were evaluated to determine their prognostic significance. Two-year overall survival was achieved in 67 per cent of all patients and 55 per cent of patients were relapse-free at 2 years. All except 10 patients, with identified French-American-British L3 morphology were treated with the modified Berlin-Frankfurt-Munster 78 treatment protocol. Univariate analyses of failure rate conferred age, sex, white cell count and hemoglobin level as potentially significant prognostic factors. All four presenting features retained their prognostic strength in a multivariate analysis. Race, platelet count, morphological subtype, liver/spleen size, lymphadenopathy, central nervous system and mediastinal mass involvement did not show any significant effect on treatment outcome. The 2-year survival rate was significantly different with regard to age, white cell count and hemoglobin level. However, sex was not significantly related to overall survival. These prognostic factors may have implications on future stratification of risk-adjusted initial treatment in the management of childhood ALL. Our analysis of Malaysian children is similar to what could be predicted based on previous studies in other populations.
Anthracycline-Free Protocol for Favorable-Risk Childhood ALL: A Noninferiority Comparison Between Malaysia-Singapore ALL 2003 and ALL 2010 Studies

Ariffin H, Chiew EKH, Oh BLZ, Lee SHR, Lim EH, Kham SKY, et al.

J Clin Oncol, 2023 Jul 10;41(20):3642-3651.
PMID: 37276496 DOI: 10.1200/JCO.22.02347

PURPOSE: To investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m2 of anthracyclines.
PATIENTS AND METHODS: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts.
RESULTS: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively (P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% (P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively (P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004).
CONCLUSION: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.
Bone marrow and stem cell transplantation: Malaysian experience

Gan G, Teh A, Chan L, Cheong S, Chang K, Ibrahim H

Bone Marrow Transplant, 2008 Aug;42 Suppl 1:S103-S105.
PMID: 18724278 DOI: 10.1038/bmt.2008.129

Malaysia conducted the first BMT in the country in 1987. Since then, there have been 1155 transplantations performed in a total of eight transplant centres. A majority of the transplantations were allogeneic, including myeloablative and nonmyeloablative. A vast majority of donors are HLA identical siblings. The mean age of transplanted patients was 26 years. The major reason for transplantation was hematological malignancies. The overall survival was 60% for allogeneic transplantation and 52% for autologous transplantation. The most common cause of death in transplanted patients was the underlying disease followed by infection-related complications. Currently, the government is expanding the existing public cord blood bank as well as the local donor registry.
Bone marrow transplantation in Malaysia

Lin HP, Chan LL, Tan A, Ariffin WA, Lam SK

Bone Marrow Transplant, 1994 Jun;13(6):725-9.
PMID: 7920303

The sole BMT centre in Malaysia caters only for children. Since 1987, 89 transplants have been performed using reverse barrier nursing techniques. The overall survival rate is 73% with the majority of survivors leading normal lives. The early and late infection rates of 46% and 13%, respectively, are comparable to those of other centres. Although the early septicaemia rate is 36% the immediate mortality rate is < 10%. GVHD is less frequent and severe and the interstitial pneumonitis rate lower than that in the West. The average cost of US $8000 per transplant is much lower than the cost of a transplant performed overseas. Thus we believe that our paediatric BMT programme is simple and cost-effective.
Characterisation and confirmation of rare beta-thalassaemia mutations in the Malay, Chinese and Indian ethnic groups in Malaysia

Tan JA, Chin PS, Wong YC, Tan KL, Chan LL, George E

Pathology, 2006 Oct;38(5):437-41.
PMID: 17008283

In Malaysia, about 4.5% of the Malay and Chinese populations are heterozygous carriers of beta-thalassaemia. The initial identification of rare beta-globin gene mutations by genomic sequencing will allow the development of simpler and cost-effective PCR-based techniques to complement the existing amplification refractory mutation system (ARMS) and gap-PCR used for the identification of beta-thalassaemia mutations.
Fulltext Characterisation of Bacterial Isolates from Infected Post-Operative Patients in a Malaysian Tertiary Heart Care Centre

Yong YK, Wen NCM, Yeo GEC, Chew ZX, Chan LL, Md Zain NZ, et al.

Int J Environ Res Public Health, 2021 09 17;18(18).
PMID: 34574752 DOI: 10.3390/ijerph18189828

Several bacterial species cause post-operative infections, which has been a critical health concern among hospital patients. Our study in this direction is a much-needed exploratory study that was carried out at the National Heart Institute (IJN) of Malaysia to examine the virulence properties of causative bacteria obtained from postoperative patients. The bacterial isolates and data were provided by the IJN. Antibiotic resistance gene patterns, and the ability to form biofilm were investigated for 127 isolates. Klebsiella pneumoniae (36.2%) was the most common isolate collected, which was followed by Pseudomonas aeruginosa (26%), Staphylococcus aureus (23.6%), Streptococcus spp. (8.7%) and Acinetobacter baumannii (5.5%). There were 49 isolates that showed the presence of multidrug resistance genes. The mecA gene was surprisingly found in methicillin-susceptible S. aureus (MSSA), which also carried the ermA gene from those erythromycin-susceptible strains. The phenotypic antibiotic resistance profiles varied greatly between isolates. Findings from the biofilm assay revealed that 44 of the 127 isolates demonstrated the ability to produce biofilms. Our findings provide insights into the possibility of some of these bacteria surviving under antibiotic stress, and some antibiotic resistance genes being silenced.
Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox

Viprakasit V, Ibrahim H, Ha SY, Ho PJ, Li CK, Chan LL, et al.

Int J Hematol, 2011 Mar;93(3):319-328.
PMID: 21374076 DOI: 10.1007/s12185-011-0789-8

Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.
Clinical features and treatment outcome of children with myeloid antigen coexpression in B-lineage acute lymphoblastic leukemia: a study of 151 Malaysian children

Ng SM, Ariffin WA, Lin HP, Chan LL, Chin YM

J Trop Pediatr, 2000 Apr;46(2):73-8.
PMID: 10822932

The purpose of the study was to evaluate the incidence of myeloid antigen coexpression and its prognostic significance in childhood acute lymphoblastic leukemia (ALL) in Malaysia. A retrospective study was conducted of all ALL cases (< or = 12 years old) diagnosed and treated in University Hospital, Kuala Lumpur, Malaysia between 1 January 1992 and 30 May 1995, with available immunophenotype data. Presenting features and treatment outcome of 39 B-lineage ALL patients with myeloid antigen coexpression (My+B) were compared with 112 B-lineage ALL patients without myeloid antigen coexpression (My-B) for similarity in demographic, clinical and laboratory features and their treatment outcome. My+B and My-B patients were treated with a uniform treatment protocol. Myeloid antigen coexpression was defined as more than 30% isolated leukemic cells positive for CD13 and/or CD33. The ages at diagnoses ranged from 2 months to 12 years. Median age was 4 years. The incidence of myeloid antigen coexpression was 23 per cent. Univariate analyses showed that presenting features were similar between My+B and My-B with regard to age, sex, race, FAB morphology, white cell count, hemoglobin level, platelet count, liver/spleen size, central nervous system or mediastinal involvement, presence of lymphadenopathy, and proportion of blast cells detected in the marrow. Treatment outcome were not significant between the two groups. The 2-year event free survival was achieved in 44 per cent of My+B and 57 per cent of My-B (p = 0.11). The 2-year overall survival rates were 62 per cent for My+B vs. 77 per cent for My-B (p = 0.08). This study demonstrates that myeloid antigen coexpression is fairly common and constitutes 23 per cent of childhood ALL within the Malaysian population and that it is not an adverse risk factor in childhood ALL.
Controlled delivery of the antiprotozoal agent (tinidazole) from intravaginal polymer matrices for treatment of the sexually transmitted infection, trichomoniasis

Fernando HV, Chan LL, Dang N, Santhanes D, Banneheke H, Nalliah S, et al.

Pharm Dev Technol, 2019 Mar;24(3):348-356.
PMID: 29799300 DOI: 10.1080/10837450.2018.1481430

Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to -80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.4 to 3.9% (w/w), when the drug concentration in the starting PCL solution was raised from 10 to 20% (w/w), giving rise to drug loading efficiencies up to 20%. Rapid 'burst release' of 30% of the tinidazole content was recorded over 24 h when the PCL matrices were immersed in simulated vaginal fluid. Gradual drug release occurred over the next 6 days resulting in delivery of around 50% of the tinidazole load by day 7 with the released drug retaining antiprotozoal activity at levels almost 50% that of the 'non-formulated' drug in solution form. Basic modelling predicted that the concentration of tinidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration against Trichomonas vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of antiprotozoal agents in the treatment and prevention of sexually transmitted infections.
Cure of beta-thalassaemia major by umbilical cord blood transplantation--a case report of Malaysia's first cord blood transplantation

Chan LL, Lin HP

J Trop Pediatr, 1999 Aug;45(4):243-5.
PMID: 10467839

A 25-month-old boy with beta-thalassaemia major was presented with an opportunity for umbilical cord blood transplantation when his unborn sibling was diagnosed in utero to be a beta-thalassaemia carrier and also human leucocyte antigen compatible. A barely adequate amount of cord blood was collected at the birth of his sibling and infused into the patient after appropriate chemo-conditioning. Engraftment occurred without major complications. The subject is now alive and well 9 months post-transplant, thus marking our first success in umbilical cord blood transplantation.
Fulltext Effects of substratum and depth on benthic harmful dinoflagellate assemblages

Lee LK, Lim ZF, Gu H, Chan LL, Litaker RW, Tester PA, et al.

Sci Rep, 2020 07 09;10(1):11251.
PMID: 32647125 DOI: 10.1038/s41598-020-68136-6

Microhabitats influence the distribution and abundance of benthic harmful dinoflagellate (BHAB) species. Currently, much of the information on the relationships between BHABs and microhabitat preferences is based on non-quantitative anecdotal observations, many of which are contradictory. The goal of this study was to better quantify BHAB and microhabitat relationships using a statistically rigorous approach. Between April 2016 to May 2017, a total of 243 artificial substrate samplers were deployed at five locations in the Perhentian Islands, Malaysia while simultaneous photo-quadrat surveys were performed to characterize the benthic substrates present at each sampling site. The screen samplers were retrieved 24 h later and the abundances of five BHAB genera, Gambierdiscus, Ostreopsis, Coolia, Amphidinium, and Prorocentrum were determined. Substrate data were then analyzed using a Bray-Curtis dissimilarity matrix to statistically identify distinct microhabitat types. Although BHABs were associated with a variety of biotic and abiotic substrates, the results of this study demonstrated differing degrees of microhabitat preference. Analysis of the survey results using canonical correspondence analysis explained 70.5% (horizontal first axis) and 21.6% (vertical second axis) of the constrained variation in the distribution of various genera among microhabitat types. Prorocentrum and Coolia appear to have the greatest range being broadly distributed among a wide variety of microhabitats. Amphidinium was always found in low abundances and was widely distributed among microhabitats dominated by hard coral, turf algae, sand and silt, and fleshy algae and reached the highest abundances there. Gambierdiscus and Ostreopsis had more restricted distributions. Gambierdiscus were found preferentially associated with turf algae, hard coral and, to a lesser extent, fleshy macroalgae microhabitats. Ostreopsis, almost always more abundant than Gambierdiscus, preferred the same microhabitats as Gambierdiscus and were found in microbial mats as well. With similar habitat preferences Ostreopsis may serve as an indicator organism for the presence of Gambierdiscus. This study provides insight into how BHAB-specific microhabitat preferences can affect toxicity risks.
Fulltext Enzyme replacement therapy for Gaucher Disease: the only experience in Malaysia

Chan LL, Lin HP

Med J Malaysia, 2002 Sep;57(3):348-52.
PMID: 12440275 MyJurnal

Gaucher Disease may now be treated with enzyme replacement therapy (ERT) or bone marrow transplantation (BMT). Both have their advantages and disadvantages. Results with BMT are curative when successful but limited by the scarcity of an appropriate donor. ERT offers very good relief of symptoms but treatment is lifelong and cost of treatment exorbitant. Patients in developing countries are particularly disadvantaged and management remains a dilemma for both doctor and patient.
Erratum to: Should All Children Admitted with Community Acquired Pneumonia have Blood Cultures Taken?

Lai EM, Nathan AM, de Bruyne JA, Chan LL

Indian J Pediatr, 2015 Jun;82(6):579.
PMID: 25640069 DOI: 10.1007/s12098-015-1698-2

Erratum to: Indian J Pediatr DOI 10.1007/s12098-014-1565-6. In the original article, acknowledgement to a grant was missed. Below is the acknowledgement section. This study was partly funded by the UMR grant (no. UM.TNC2/RC/HTM/RP026-14HTM) awarded to AMN and JAdeB by University Malaya. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Haematopoietic stem cell transplantation for inborn errors of immunity: 25-year experience from University of Malaya Medical Centre, Malaysia

Ariffin H, Ab Rahman S, Jawin V, Foo JC, Amram NF, Mahmood NM, et al.

J Paediatr Child Health, 2020 Mar;56(3):379-383.
PMID: 31479560 DOI: 10.1111/jpc.14621

AIM: Inborn errors of immunity (IEI) comprise a heterogeneous group of disorders of the immune system, most of which are curable by haematopoietic stem cell transplantation (HSCT). We present a 25-year audit of HSCT for IEI at a tertiary-level academic hospital in Malaysia.
METHODS: Review of medical records of all cases of IEI who underwent HSCT between January 1993 and December 2018 at our centre. Diagnoses, complications, HSCT protocols and outcome data were studied.
RESULTS: There were 20 patients (19 boys) with a median age at diagnosis of 11 months (range: 2 months to 12 years). Eleven of 19 (58%) had malnutrition at presentation. Donor sources were variable: 13 (65%) matched sibling donor (MSD), 4 (20%) human leukocyte antigen-haploidentical donor (HD) and 3 (15%) matched unrelated donor (MUD). Conditioning regimens were physician-dependent and adapted to each patient's clinical status. Grades III-IV acute graft-versus-host disease occurred in two of three cases who received MUD grafts, 50% in those who received HD, and 8% in the MSD group. Transplant-related mortality at day +100 was 5%. With a median follow-up of 7.5 years, 18 (90%) patients are alive and free of infections.
CONCLUSION: Outcome of HSCT for IEI in our centre is comparable with international reports. HSCT results using HD and MUD grafts are also good despite challenges from acute graft-versus-host disease, providing a feasible alternative for patients without matched donors.
Haemophagocytic lymphohistiocytosis in Malaysian children

Ariffin H, Lum SH, Cheok SA, Shekhar K, Ariffin WA, Chan LL, et al.

J Paediatr Child Health, 2005 Mar;41(3):136-9.
PMID: 15790325

To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre.
Fulltext Identification and ultrastructural characterization of Acanthamoeba bacterial endocytobionts belonging to the Alphaproteobacteria class

Chan LL, Mak JW, Ambu S, Chong PY

PLoS One, 2018;13(10):e0204732.
PMID: 30356282 DOI: 10.1371/journal.pone.0204732

The detection and identification of two endocytobiotic bacterial strains, one affiliated to the "Candidatus Caedibacter acanthamoebae"/"Ca. Paracaedimonas acanthamoeba", and another to the endosymbiont of Acanthamoeba UWC8 and "Ca. Jidaibacter acanthamoeba" are described. For endocytobiont screening, we developed a PCR method with a set of broad-range bacterial 16S rRNA primers to substitute the commonly used but technically demanding fluorescent in situ hybridization technique. Our PCR test alone without sequencing failed to discriminate the endocytobiont-containing and endocytobiont-free Acanthamoeba sp. due to the presence of mismatched primers to host mitochondrial DNA. We highlighted the need to perform bacterial primer checking against the Acanthamoeba genome to avoid false positive detection in PCR. Although the genetic aspect of "Ca. Caedibacter acanthamoebae"/"Ca. Paracaedimonas acanthamoeba" and the endosymbiont of Acanthamoeba UWC8/"Ca. Jidaibacter acanthamoeba" are well studied, knowledge pertaining to their morphologies are quite vague. Hence, we used transmission electron microscopy to examine our endocytobionts which are affiliated to previously described intracellular bacteria of Acanthamoeba sp. We used good-quality TEM images for the localization and the fate of the current endocytobionts inside different life stages of the hosts. Furthermore, to the best of our knowledge, our TEM findings are the first to provide morphological evidence for the clearance of defective Acanthamoeba endocytobionts via an autophagic-like process.
Fulltext Identification of Comprehensive Geriatric Assessment Based Risk Factors for Malnutrition in Elderly Asian Cancer Patients

Tan T, Ong WS, Rajasekaran T, Nee Koo K, Chan LL, Poon D, et al.

PLoS One, 2016;11(5):e0156008.
PMID: 27231951 DOI: 10.1371/journal.pone.0156008

PURPOSE: Elderly cancer patients are at increased risk for malnutrition. We aim to identify comprehensive geriatric assessment (CGA) based clinical factors associated with increased nutritional risk and develop a clinical scoring system to identify nutritional risk in elderly cancer patients.
PATIENTS AND METHODS: CGA data was collected from 249 Asian patients aged 70 years or older. Nutritional risk was assessed based on the Nutrition Screening Initiative (NSI) checklist. Univariate and multivariate logistic regression analyses were applied to assess the association between patient clinical factors together with domains within the CGA and moderate to high nutritional risk. Goodness of fit was assessed using Hosmer-Lemeshow test. Discrimination ability was assessed based on the area under the receiver operating characteristics curve (AUC). Internal validation was performed using simulated datasets via bootstrapping.
RESULTS: Among the 249 patients, 184 (74%) had moderate to high nutritional risk. Multivariate logistic regression analysis identified stage 3-4 disease (Odds Ratio [OR] 2.54; 95% CI, 1.14-5.69), ECOG performance status of 2-4 (OR 3.04; 95% CI, 1.57-5.88), presence of depression (OR 5.99; 95% CI, 1.99-18.02) and haemoglobin levels <12 g/dL (OR 3.00; 95% CI 1.54-5.84) as significant independent factors associated with moderate to high nutritional risk. The model achieved good calibration (Hosmer-Lemeshow test's p = 0.17) and discrimination (AUC = 0.80). It retained good calibration and discrimination (bias-corrected AUC = 0.79) under internal validation.
CONCLUSION: Having advanced stage of cancer, poor performance status, depression and anaemia were found to be predictors of moderate to high nutritional risk. Early identification of patients with these risk factors will allow for nutritional interventions that may improve treatment tolerance, quality of life and survival outcomes.
Immunohistochemical expression of p53 proteins in Wilms' tumour: a possible association with the histological prognostic parameter of anaplasia

Cheah PL, Looi LM, Chan LL

Histopathology, 1996 Jan;28(1):49-54.
PMID: 8838120

Wilms' tumour (nephroblastoma) has been associated with chromosomal abnormalities at the 11p13, 11p15 and 16q regions. A study into the possibility of mutations occurring within p53, the ubiquitous adult tumour suppressor gene, in Wilms' tumour was carried out. Thirty-eight cases were studied. Of these 36 were categorised into the favourable histology group and two into the unfavourable histology group based on the National Wilms' Tumour Study criteria. Archival formalin-fixed, paraffin-embedded tissue sections from each case were stained with a polyclonal (AB565:Chemicon) and a monoclonal (DO7:Dako) antibody raised against p53 protein using a peroxidase-labelled streptavidin biotin kit (Dako). 'Cure' (disease-free survival of 60 months or longer) was documented in 39% of cases with favourable histology tumours. Eleven percent in this group succumbed to the disease. Both cases with unfavourable histology died. Four out of 36 (11%) tumours with favourable histology demonstrated weak to moderate staining with both AB565 and DO7 in more than 75% of tumour cells. In contrast, p53 protein expression in unfavourable histology tumours was significantly increased compared with the favourable histology group (P = 0.021) with both cases demonstrating immunopositivity in > 75% of tumour cells when stained with AB565 and DO7. The intensity of staining ranged from moderate to strong in both cases. It appears from this preliminary study that the immunohistochemical expression of p53 protein in Wilms' tumour, presumably a result of mutation in the p53 tumour suppressor gene, correlates with histological classification, histological categorisation being one of the useful features in the prognostic assessment of Wilms' tumours.
Incidence of fragility hip fracture across the Asia-pacific region: A systematic review

Chan LL, Ho YY, Taylor ME, Mcveigh C, Jung S, Armstrong E, et al.

Arch Gerontol Geriatr, 2024 Mar 21;123:105422.
PMID: 38579379 DOI: 10.1016/j.archger.2024.105422

PURPOSE: This systematic review aimed to update fragility hip fracture incidences in the Asia Pacific, and compare rates between countries/regions.
METHOD: A systematic search was conducted in four electronic databases. Studies reporting data between 2010 and 2023 on the geographical incidences of hip fractures in individuals aged ≥50 were included. Exclusion criteria were studies reporting solely on high-trauma, atypical, or periprosthetic fractures. We calculated the crude incidence, age- and sex-standardised incidence, and the female-to-male ratio. The systematic review was registered with PROSPERO (CRD42020162518).
RESULTS: Thirty-eight studies were included across nine countries/regions (out of 41 countries/regions). The crude hip fracture incidence ranged from 89 to 341 per 100,000 people aged ≥50, with the highest observed in Australia, Taiwan, and Japan. Age- and sex-standardised rates ranged between 90 and 318 per 100,000 population and were highest in Korea and Japan. Temporal decreases in standardised rates were observed in Korea, China, and Japan. The female-to-male ratio was highest in Japan and lowest in China.
CONCLUSION: Fragility hip fracture incidence varied substantially within the Asia-Pacific region. This observation may reflect actual incidence differences or stem from varying research methods and healthcare recording systems. Future research should use consistent measurement approaches to enhance international comparisons and service planning.

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